The intravenous drug 2,6-diisopropylphenol (propofol) is a proven general anesthetic which is widely used in many surgical and critical care settings for the purpose of general anesthesia or conscious sedation (Krasowski et al., J Pharm Exp Therap 297:338-351 (2001)). The broad appeal and popularity of propofol is related to the rapid induction and rapid elapse of anesthesia. The target steady-state concentration range of propofol in blood is between 0.25-2.0 μg/mL or 1-12 μM. In general, these target values are set by constant infusion rates ranging between 0.3-3.0 mg/kg/h.
Propofol infusion syndrome (PRIS) is a well-known adverse event that is associated with high doses and long term use of propofol (Zaccheo et al., Crit Care Nurse 28:18-25 (2008); McKeage and Perry, CNS Drugs 17:235-272 (2003)). It can lead to cardiac and renal failure in critically ill patients and is often fatal. Successful treatment of PRIS requires early recognition and immediate discontinuation of propofol infusion. The propofol related death of Michael Jackson has recently brought the safety of propofol administration into the limelight and underlined the importance of monitoring propofol during anesthesia.
Target-controlled infusion anesthesia (TCIA) aims to provide stable, user-defined, blood concentrations of anesthetic drugs using small-platform delivery systems. The infusion rate of the drug is set by algorithms utilizing population-based pharmacokinetic data and individual patient biometrics (Schnider and Minto, Anaesthesia 63:206 (2008); Coppens et al., Brit J Anaesth 104:452-458 (2010); Struys et al., Anesthesiology 100:640-647 (2004); Stonell et al., Anaesthesia 61:240-247 (2006); Absalom et al., Brit J Anaesth 103:26-37 (2009); Absalom et al., Brit J Anaesth 104:261-264 (2010)). TCIA of propofol is now widely used outside of North America. However, the U.S. Food and Drug Administration (FDA) has not approved TCIA for use in the United States despite numerous studies that have documented excellent patient safety profiles for various forms of anesthesia using this approach (Casati et al., Can J Anaesth 46:235-239 (1999); Chen et al., Eur J Anesth 26:928-935 (2009); Leslie et al., Cochrane Db Syst Rev (2008)). Measuring propofol levels in real-time during anesthesia and correlating blood levels with efficacy data would greatly enhance the safety of propofol delivery and potentially permit the approval of “closed-loop TCIA”. To date, real-time measurements of propofol concentration in blood and other biological fluids have been elusive. Instead, most of the efforts are focused on monitoring propofol in the exhaled breath (Grossherr et al., Brit J Anaesth 102:608-613 (2009); Harrison et al., Brit J Anaesth 91:797-799 (2003); Grossherr et al., Anesthesiology 104:786-790 (2006); Miekisch et al., Clin Chim Acta 395:32-37 (2008)) and finding the correlation between the exhaled breath and plasma values (Grossherr et al., Anesthesiology 104:786-790 (2006).
The difficulties for electrochemical quantification of propofol in aqueous solution have been discussed in the literature (Langmaier et al., Anal. Chim. Acta 704:63-67 (2011)). While propofol can be oxidized electrochemically, similar to other phenolic compounds (Azevedo et al., J. Electroanal. Chem. 658:38-45 (2011); Kim et al., Anal. Chim. Acta 479:143-150 (2003); Spataru et al., J. Hazard. Mater. 180:777-780 (2010); Yin et al., Microchim. Acta 175:39-46 (2011); Yin et al., Electrochim. Acta 56:2748-2753 (2011); Zejli et al., Anal. Chim. Acta 612:198-203 (2008)), product(s) from the electrochemical oxidation and coupled reactions may deposit to the electrode surface causing immediate passivation or gradual electrode fouling. Although the detrimental effect of electrode fouling could be minimized, the previously reported detection limit (3.2 μM) and selectivity remained inadequate for monitoring propofol in biological samples. Due to the limited selectivity of voltammetric methods, electrochemical propofol sensors are mainly used as detectors in chromatographic separation (Mazzi et al., J. Chromatogr-Biomed. 528:537-541 (1990); Pissinis et al., J. Liq. Chromatogr. R. T 30:1787-1795 (2007); Trocewicz et al., J. Chromatogr. B. 685:129-134 (1996)). It is therefore desirable to identify an improved electrochemical sensor that can detect propofol as well as other electrochemically active drugs or metabolites in biological samples across their physiological and therapeutic ranges.
The present invention is directed to overcoming these and other deficiencies in the art.